Andrzej Witek

Long-term impact of surgical repair for stress urinary incontinence on female sexual functions, distress and behaviours

AIMS AND OBJECTIVES To evaluate sexual functions, distress and behaviours in women who underwent surgical repair of stress urinary incontinence (SUI) in long-term follow-up. BACKGROUND Contemporary management of SUI includes conservative therapy and surgical repair - the choice of treatment modality depends on the severity of symptoms. If conservative treatment fails, surgical correction is necessary. The outcomes of the surgery for SUI and their influence on sexual functions are satisfactory in short-term follow-up. DESIGN A total of 50 women diagnosed with SUI according to International Continence Society standards were included in the study. The patients were qualified for surgical procedures such as: transobturator suburethral tape (TOT) (n = 35), Perigee (n = 6) or MiniArc (n = 9). METHODS Sexual functions and behaviours were evaluated prior to the operation and 1-3 years postoperatively in all patient using Female Sexual Function Index (FSFI) and non-validated questions. RESULTS The mean time after the operation was 1·96 ± 0·83 years. Postoperatively, all women reported significant reduction of urinary incontinence symptoms. According to DSM-IV criteria, female sexual dysfunctions were diagnosed in 12% of females after the urogenital operation. However, sexual complaints (FSFI scores equal or <26·55 points) without distress were reported by 62% of the patients. The comparison of sexual complaints declared prior to and after the operation showed significant differences in the prevalence of decreased desire, decreased arousal and decreased orgasm frequency. In addition, we documented significant improvement of sexual attractiveness and sexual life evaluation after the SUI operation. CONCLUSIONS Surgical repair for SUI improves female sexual functions and reduces sexual distress, as observed in a long-term follow-up. RELEVANCE TO CLINICAL PRACTICE Sexual functions, distress and behaviours in women who underwent surgical repair of SUI; the impact of SUI female quality of life as well as on sexual functions.

Estrogen Receptor βΔ6 (ERβΔ6) Isoform in Human Endometrial Hyperplasia and Adenocarcinoma

Estrogen receptor (ER)-β may play a significant role in estrogen action in several human tissues. Estrogen receptor β may act as a transdominant repressor of ERα transcriptional activity trough heterodimers form. Estrogen receptor messenger RNA (mRNA) variants also may be involved in various diseases, including endometrial cancer. The absence of estrogen receptors has often correlated with poor prognosis of endometrial tumors. The objective of the study was to determine the number of mRNA ERβΔ6 and (wtERβ) in 1 µg total RNA obtained from tissues of normal, hyperplastic endometrium, and endometrial adenocarcinoma. This study was designed to evaluate possible differences in the ERβΔ6 and wtERβ messenger RNA (mRNA) level in the normal, hyperplastic endometrium, and endometrial endometrioid adenocarcinoma (G1, G2 morphological degree). Adenocarcinoma showed significantly lower ERβΔ6 mRNA level than proliferative (p = 0.032) and secretory (p = 0.01) endometrium. A decrease of mRNA wtERβ in endometrial adenocarcinoma (p = 0.006) also was observed.

Changes in expression of cartilaginous genes during chondrogenesis of Wharton's jelly mesenchymal stem cells on three-dimensional biodegradable poly(L-lactide-co-glycolide) scaffolds

BackgroundIn cartilage tissue regeneration, it is important to develop biodegradable scaffolds that provide a structural and logistic template for three-dimensional cultures of chondrocytes. In this study, we evaluated changes in expression of cartilaginous genes during in vitro chondrogenic differentiation of WJ-MSCs on PLGA scaffolds.MethodsThe biocompatibility of the PLGA material was investigated using WJ-MSCs by direct and indirect contact methods according to the ISO 10993–5 standard. PLGA scaffolds were fabricated by the solvent casting/salt-leaching technique. We analyzed expression of chondrogenic genes of WJ-MSCs after a 21-day culture.ResultsThe results showed the biocompatibility of PLGA and confirmed the usefulness of PLGA as material for fabrication of 3D scaffolds that can be applied for WJ-MSC culture. The in vitro penetration and colonization of the scaffolds by WJ-MSCs were assessed by confocal microscopy. The increase in cell number demonstrated that scaffolds made of PLGA copolymers enabled WJ-MSC proliferation. The obtained data showed that as a result of chondrogenesis of WJ-MSCs on the PLGA scaffold the expression of the key markers collagen type II and aggrecan was increased.ConclusionsThe observed changes in transcriptional activity of cartilaginous genes suggest that the PLGA scaffolds may be applied for WJ-MSC differentiation. This primary study suggests that chondrogenic capacity of WJ-MSCs cultured on the PLGA scaffolds can be useful for cell therapy of cartilage.

Identification of a gene expression profile associated with the regulation of angiogenesis in endometrial cancer

The publication of the human genome sequence provided direction in the search for novel diagnostic and therapeutic methods for the treatment of human diseases. The aim of the present study was to investigate the hypothesis that the expression profile of genes involved in the regulation of angiogenesis may be a marker in endometrial cancer that facilitates the diagnosis and prognosis of patients, as well as the identification of novel therapeutic targets. The current study included 36 patients with grade (G) 1 to 3 endometrial cancer, and a control group of patients consisting of females that qualified for the removal of the uterus. Out of these, 28 samples (control, 3; G1, 7; G2, 12; and G3, 6) were selected for microarray analysis. Molecular analysis of the endometrial samples involved the extraction of total RNA, purification of the obtained extracts and subsequent analysis of the gene expression profiles using an oligonucleotide microarray technique (GeneChip® Human Genome U133A plates). The results indicated that the mRNA expression profile of genes involved in the regulation of angiogenesis varies depending on the degree of histological differentiation of endometrial adenocarcinoma. Similar results were obtained from descriptive statistics characterizing the expression profile of 691 mRNAs associated with the regulation of angiogenesis in the groups of patients with endometrial adenocarcinoma. In addition, the results of the present study indicated that neuropilin2 (NRP2) may serve an important role in the activity of endothelial cells, and may affect vascular endothelial growth factor, and potentially plexins and integrins via regulation of their functions. An understanding of how these proteins interact remains to be determined; however, elucidating these interactions may provide an explanation for the mechanisms underlying angiogenesis. In conclusion, the results of the present study suggest that NRP2 may be a valuable target for investigation in future pharmacological studies involving angiogenesis in endometrial cancer.

Bronchial hyperreactivity in perimenstrual asthma is associated with increased Th-2 response in lower airways

BACKGROUND Perimenstrual asthma (PMA) is a commonly observed, usually difficult-to-treat asthma phenotype. The mechanisms underlying this phenomenon remain unexplained. The aim of the study was to assess the degree of airway hyperresponsiveness and its relationship to proinflammatory cytokines concentration in lower airways of PMA compared to non-PMA patients. METHODS Premenopausal women with regular menstrual cycles diagnosed as: PMA (n=12), non-PMA asthmatics (n=9), and healthy controls (n=10) were prospectively followed for 10 weeks over two consecutive menstrual cycles. The bronchial responsiveness (BR) test to methacholine was performed in each subject prior to the study. The serum for total immunoglobulin E (IgE) concentrations was taken and sputum was induced in the 26th day of each of the two cycles. Sputum concentration of eotaxin, IL-4 and IL-10 were measured by ELISA. RESULTS Levels of BR to metacholine as well, as total blood IgE concentrations in PMA subjects were significantly higher than in non-PMA asthmatics and healthy controls (P=0.001, P=0.022 respectively) and correlated with each other (P=0.030; r =-0.65). Sputum eotaxin and IL-4 concentrations in luteal phase were increased in PMA patients when compared with non-PMA asthmatics (P=0.016; P=0.041, respectively) and healthy subjects (P<0.001 both cytokines). No differences for the sputum levels of IL-10 among studied groups were seen. CONCLUSIONS BR level in perimenstrual asthma is higher than in non-PMA asthmatics and correlates with increased total IgE serum concentration. The increased level of BR in PMA patients is associated with a shift in the type-1/type-2 cytokine balance toward a type-2 response.

Comparison of gene expression of mitogenic kinin path in adherent and non-adherent CD 34-stem cells using oligonucleotide microarrays.

One of the more interesting cells present in the umbilical cord blood - as far as their potential clinical use is concerned - are stem cells not presenting the CD34 antigen. These are the pluripotential cells with their biological properties similar to mesenchymal stem cells, with the ability to differentiate into such tissue types as bone, cartilage, nervous (to some extent), glia and muscle. The authors compared the activity of genes coding the proteins in mitogenic signal paths activated by kinin receptors using oligonucleotide microarrays in adherent and non-adherent CD 34- cells derived from umbilical cord blood. In the linear regression model with a 95% prognosis area for differentiating genes outside this area, the following genes were selected: c-jun (present in 3 isoforms) and c-fos. The fos and jun genes create the AP-1 transcriptive factor which regulates the expression of genes taking part in numerous cellular processes, including the cell cycle and mitosis. The obtained results shed some light on the molecular processes behind the MSC proliferation and are a starting point for further studies on the mesenchymal stem cell biology.